Revisiting the Notion of Deleterious Sweeps

It has previously been shown that, conditional on its fixation, the time to fixation of a semi-dominant deleterious autosomal mutation in a randomly mating population is the same as that of an advantageous mutation. This result implies that deleterious mutations could generate selective sweep-like effects. Although their fixation probabilities greatly differ, the much larger input of deleterious relative to beneficial mutations suggests that this phenomenon could be important. We here examine how the fixation of mildly deleterious mutations affects levels and patterns of polymorphism at linked sites - both in the presence and absence of interference amongst deleterious mutations - and how this class of sites may contribute to divergence between-populations and species. We find that, while deleterious fixations are unlikely to represent a significant proportion of outliers in polymorphism-based genomic scans within populations, minor shifts in the frequencies of deleterious mutations can influence the proportions of private variants and the value of FST after a recent population split. As sites subject to deleterious mutations are necessarily found in functional genomic regions, interpretations in terms of recurrent positive selection may require reconsideration.

Revisiting the notion of deleterious sweeps

ABSTRACTIt has previously been shown that, conditional on its fixation, the time to fixation of a semi-dominant deleterious autosomal mutation in a randomly mating population is the same as that of an advantageous mutation. This result implies that deleterious mutations may generate selective sweep effects. Although their fixation probabilities greatly differ, the much larger input of deleterious relative to beneficial mutations suggests that this phenomenon could be important. We here examine how the fixation of mildly deleterious mutations affects levels and patterns of polymorphism at linked sites, and how this class of sites may contribute to divergence between-populations and species. We find that, while deleterious sweeps are unlikely to represent a significant proportion of outliers in polymorphism-based genomic scans within populations, minor shifts in the frequencies of deleterious mutations can influence the proportions of private variants and the value of FST after a recent population split. As sites subject to deleterious mutations are necessarily found in functional genomic regions, interpretations in terms of recurrent positive selection may require reconsideration.

Considering Genomic Scans for Selection as Coalescent Model Choice

First inspired by the seminal work of Lewontin and Krakauer (1973. Distribution of gene frequency as a test of the theory of the selective neutrality of polymorphisms. Genetics 74(1):175–195.) and Maynard Smith and Haigh (1974. The hitch-hiking effect of a favourable gene. Genet Res. 23(1):23–35.), genomic scans for positive selection remain a widely utilized tool in modern population genomic analysis. Yet, the relative frequency and genomic impact of selective sweeps have remained a contentious point in the field for decades, largely owing to an inability to accurately identify their presence and quantify their effects—with current methodologies generally being characterized by low true-positive rates and/or high false-positive rates under many realistic demographic models. Most of these approaches are based on Wright–Fisher assumptions and the Kingman coalescent and generally rely on detecting outlier regions which do not conform to these neutral expectations. However, previous theoretical results have demonstrated that selective sweeps are well characterized by an alternative class of model known as the multiple-merger coalescent. Taken together, this suggests the possibility of not simply identifying regions which reject the Kingman, but rather explicitly testing the relative fit of a genomic window to the multiple-merger coalescent. We describe the advantages of such an approach, which owe to the branching structure differentiating selective and neutral models, and demonstrate improved power under certain demographic scenarios relative to a commonly used approach. However, regions of the demographic parameter space continue to exist in which neither this approach nor existing methodologies have sufficient power to detect selective sweeps.

Genetic architecture of a body color cline in Drosophila americana

Phenotypic variation within a species is often structured geographically in clines. In Drosophila americana, a longitudinal cline for body color exists within North America that appears to be due to local adaptation. The tan and ebony genes have been hypothesized to contribute to this cline, with alleles of both genes that lighten body color found in D. americana. These alleles are similar in sequence and function to the allele fixed in D. americana’s more lightly pigmented sister species, Drosophila novamexicana. To test this hypothesis, we examined the frequency and geographic distribution of D. novamexicana-like alleles of tan and ebony in D. americana. Among alleles from over 100 strains of D. americana isolated from 21 geographic locations, we failed to identify additional alleles of tan or ebony with as much sequence similarity to D. novamexicana as the alleles previously described. However, using genetic analysis of 51 D. americana strains derived from 20 geographic locations, we identified one new allele of ebony and one new allele of tan segregating in D. americana that are functionally equivalent to the D. novamexicana allele. An additional 5 alleles of tan also showed marginal evidence of functional similarity. Given the rarity of these alleles, however, we conclude that they are unlikely to be driving the pigmentation cline. Indeed, phenotypic distributions of the 51 backcross populations analyzed indicate a more complex genetic architecture, with diversity in the number and effects of loci altering pigmentation observed both within and among populations of D. americana. This genetic heterogeneity poses a challenge to association studies and genomic scans for clinal variation, but might be common in natural populations.

Evaluating Population Genomic Candidate Genes Underlying Flowering Time in Arabidopsis thaliana Using T-DNA Insertion Lines

Population genomic scans have emerged as a powerful tool to detect regions of the genome that are potential targets of selection. Despite the success of genomic scans in identifying novel lists of loci potentially underlying adaptation, few studies proceed to validate the function of these candidate genes. In this study, we used transfer-DNA (T-DNA) insertion lines to evaluate the effects of 27 candidate genes on flowering time in North American accessions of Arabidopsis thaliana. We compared the flowering time of T-DNA insertion lines that knock out the function of a candidate gene obtained from population genomic studies to a wild type under long- and short-day conditions. We also did the same for a collection of randomly chosen genes that had not been identified as candidates. We validated the well-known effect of long-day conditions in accelerating flowering time and found that gene disruption caused by insertional mutagenesis tends to delay flowering. Surprisingly, we found that knockouts in random genes were just as likely to produce significant phenotypic effects as knockouts in candidate genes. T-DNA insertions at a handful of candidate genes that had previously been identified as outlier loci showed significant delays in flowering time under both long and short days, suggesting that they are promising candidates for future investigation.